1. Field of the Invention
This invention concerns 7-oxobicyclo[3.2.0]hept-2-en-2-carboxylic acids and derivatives thereof, a method for making them and their use as antibacterial agents either alone or in combination with .beta.-lactam antibiotics.
2. State Of The Art
The importance of .beta.-lactam antibiotics in the therapy of infectious diseases of bacterial origin in man and animals is clear. This field is reviewed by Hoover and Dunn, "The .beta.-Lactam Antibiotics", in Burger's Medicinal Chemistry (Wolff, Ed.), 4th Ed., Part II, Wiley, New York, 1979, pages 83 to 172.
Gordon et al., in Tetahedron Letters, 22 (20), 1871 to 1874 (1981) reported the syntheses of the two compounds: ##STR1## where each X is hydrogen or each X is chlorine. The authors, however, describe no utility for said compounds. Although tested for .beta.-lactamase inhibition and for DD-carboxypeptidase/transpeptidase inhibition, the compounds were ineffective. The authors concluded "that .beta.-lactam nitrogen plays a crucial role in the recognition and binding of .beta.-lactam antibiotics to these enzymes".
Meth-Conh et al., in "Carbocyclic Analogues of Penicillin", J. Chem. Soc., Chem. Commun., pages 90 to 92, 1982, describe the syntheses of compounds possessing a gem-dimethyl group and lacking unsaturation .alpha.,.beta. to the carboxylate functionality.